Table 3.
Completed, published clinical trials of HDACi monotherapy in myeloproliferative neoplasms.
| HDACi studied |
Phase | Population studied |
Efficacy | Toxicity | Author and reference |
|---|---|---|---|---|---|
| Givinostat (starting dose 50 mg bid × 24 weeks) |
IIA | 12 PV, 1 ET, 16 MF, all JAK2 V617F+ |
PV/ET: 1 CR, 6 PR; MF: 3 major responses; spleen ↓ in 75% of PV/ET and 38% of MF; pruritus resolved in most patients |
Well tolerated; dose ↓ in 10; interrupted in 15; 2 stopped due to AEs |
Rambaldi et al.(84) |
| Givinostat (50 or 100 mg/d plus MTD of hydroxyurea for maximum 24 weeks) |
II | PV (N = 44); all unresponsive to MTD of hydroxyurea |
ORR 55% at 50 mg/d; 50% at 100 mg/d; 64% and 67% had control of pruritus |
Grade 3 AEs in only 1 patient (4.5%) in each arm |
Finazzi et al.(88) |
| Vorinostat (400 mg/d × 24 weeks) |
II | 44 PV, 19 ET | Pruritus 19% to 0%; splenomegaly 50% to 27%; ↓ in JAK2 V617F allele burden in 65% |
High rate (44%) of discontinuation due to toxicity |
Andersen et al.(90) |
| Panobinostat (20, 30 or 25 mg tiw in 4- week cycles) |
I | MF (N = 18); PMF 56%, post-PV MF 28%; post- ET MF 17% |
Only 5 evaluable: 3 CI-spleen, 2 SD. Anemia improved in 2; responses deepened with time |
DLT was reversible thrombocytopenia |
Mascarenhas et al.(91) |
| Panobinostat (40 mg tiw in 4-week cycles) |
II | MF (N = 35); PMF 68.6%, post-PV MF 17.1%; post- ET MF 14.3% |
1 patient achieved an IWG-MRT response (3%) |
Poorly tolerated; diarrhea 80%, thrombocytopenia 71.4%; high early rate of discontinuation |
DeAngelo et al.(92) |
| Pracinostat (60 mg qod × 3 weeks per month) |
II | MF (N = 22) | IWG-MRT CI-anemia in 9%; 36% had clinical benefit; ↓ spleen (27%) |
Fatigue (91%); grade 3/4 neutropenia in 13%, thrombocytopenia in 21% |
Quintas- Cardama et al.(93) |
Abbreviations: PV, polycythemia vera; ET, essential thrombocythemia; MF, myelofibrosis; bid, twice daily; tiw; three times a week; qod, every other day; MTD, maximum tolerated dose; DLT, dose-limiting toxicity; AE, adverse event; SD, stable disease; CR, complete response; PR, partial response; CI, clinical improvement; IWG-MRT, International Working Group for Myelofibrosis Research and Treatment; JAK2, Janus kinase; HDACi, histone deacetylase inhibitor; PMF, primary myelofibrosis.